Ribavirin, also known as tribavirin, is an antiviral medication used to treat illness caused by respiratory syncytial virus (RSV) and hepatitis C virus (HCV) infections, as well as some viral hemorrhagic fevers. For HCV, it is used in combination with other medications, such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. It can also be used for viral hemorrhagic fevers—specifically, for Lassa fever, Crimean–Congo hemorrhagic fever, and hantavirus infections (with exceptions for Ebola or Marburg virus diseases). Ribavirin is usually taken orally (by mouth) or inhaled. Despite widespread usage, it has faced scrutiny in the 21st century because of lack of proven efficacy in treating viral infections for which it has been prescribed in the past. Its common side effects include fatigue, headache, nausea, fever, muscle pains, and an irritable mood. Serious side effects include red blood cell breakdown, liver problems, and allergic reactions. Its use during pregnancy can bring harm to the developing fetus. Effective birth control is recommended for both males and females for at least seven months during and after use. The mechanism of action of ribavirin is not entirely clear. Ribavirin was patented in 1971 and approved for medical use in 1986. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.
Medical uses Ribavirin is primarily used to treat chronic hepatitis C and viral hemorrhagic fevers (an orphan indication in most countries). Its efficacy for these purposes has been questioned in light of its Food and Drug Administration boxed warning against its use as monotherapy for chronic hepatitis C. Thus, it may be prescribed in the United States only as an adjunct to one or more other medications. Its efficacy against viruses other than HCV, including those that cause viral hemorrhagic fever, has not been conclusively demonstrated. In effect, it is not approved in the United States for treatment of viruses other than HCV.
Hepatitis C For chronic HCV infection, the oral (capsule or tablet) form of ribavirin is used only in combination with pegylated interferon alfa. Statins may improve this combination's efficacy in treating hepatitis C. When possible, genotyping of the specific viral strain is done; and ribavirin is only used as a dose-escalating adjuvant to specific combinations of genotypes and other medications. Acute hepatitis C infection (within the first 6 months) often does not require immediate treatment, as many infections eventually resolve without treatment. When the decision is made to treat acute hepatitis C, ribavirin may be used as an adjunct to several drug combinations. However, other medications are still preferred.
Viral hemorrhagic fever Ribavirin is the only known treatment for a variety of viral hemorrhagic fevers, including Lassa fever, Crimean-Congo hemorrhagic fever, Venezuelan hemorrhagic fever, and hantavirus infection, although data regarding these infections are scarce and the drug might be effective only in early stages. It is noted by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) that "Ribavirin has poor in vitro and in vivo activity against the filoviruses (Ebola and Marburg) and the flaviviruses (dengue, yellow fever, Omsk hemorrhagic fever, and Kyasanur forest disease)" The aerosol form has been used in the past to treat respiratory syncytial virus-related diseases in children, although the evidence to support this is rather weak. Despite questions surrounding its efficacy, ribavirin remains the only antiviral known to be effective in treating Lassa fever. It has been used (in combination with ketamine, midazolam, and amantadine) in treatment of rabies.
Experimental uses Experimental data indicate that ribavirin may have useful activity against canine distemper and poxviruses. Ribavirin has also been used as a treatment for herpes simplex virus. One small study found that ribavirin treatment reduced the severity of herpes outbreaks and promoted recovery, as compared with placebo treatment. Another study found that ribavirin potentiated the antiviral effect of acyclovir. Some interest has been seen in its possible use as a treatment for cancers with elevated eukaryotic translation initiation factor eIF4E, especially acute myeloid leukemia (AML) as well as in head and neck cancers. Ribavirin targeted eIF4E in AML patients in monotherapy and combination studies and this corresponded to objective clinical responses including complete remissions. Ribavirin resistance in AML patients arose leading to loss of eIF4E targeting and relapse. Resistance was caused by deactivation of ribavirin through its glucuronidation in AML cells or impaired drug entry/retention in the AML cells. There may be additional forms of ribavirin resistance displayed by cancer cells. In HPV related oropharyngeal cancers, ribavirin reduced levels of phosphorylated form of eIF4E in some patients. The best response here was stable disease but another head and neck study had more promising results.
Adverse effects
The medication has two FDA "black box" warnings: One raises concerns that use before or during pregnancy by either sex may result in birth defects in the baby, and the other is regarding the risk of red blood cell breakdown. Ribavirin should not be given with zidovudine because of the increased risk of anemia; concurrent use with didanosine should likewise be avoided because of an increased risk of mitochondrial toxicity.
Mechanisms of action It is a guanosine (ribonucleic) analog used to stop viral RNA synthesis and viral mRNA capping, thus, it is a nucleoside analog. Ribavirin is a prodrug, which when metabolized resembles purine RNA nucleotides. In this form, it interferes with RNA metabolism required for viral replication. Over five direct and indirect mechanisms have been proposed for its mechanism of action. The enzyme inosine triphosphate pyrophosphatase (ITPase) dephosphorylates ribavirin triphosphate in vitro to ribavirin monophosphate, and ITPase reduced enzymatic activity present in 30% of humans potentiates mutagenesis in hepatitis C virus.
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